Experimental study of the effect of bubbles on nucleation during batch cooling crystallization

Wohlgemuth, Kerstin; Kordylla, Anna; Ruether, Feelly; Schembecker, Gerhard

doi:10.1016/j.ces.2009.06.041

Cited by 100 publications

(85 citation statements)

References 15 publications

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“…As a result, more nuclei are formed and the nucleation rate is increased. The hypothesis of the bubble as a nucleation center considers cavitation bubbles as heterogeneous particles which lower the work needed for nucleation and hence introduce heterogeneous nucleation [16,30,42]. Finally, the segregation theory states that when a cavitation bubble collapses, the inward motion of the liquid is stopped violently by the gas recompression in the bubble.…”

Section: Nucleation In Batch Versus Flowmentioning

confidence: 99%

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

et al. 2017

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Controlling particle size is essential for crystal quality in the chemical and pharmaceutical industry. Several articles illustrate the potential of ultrasound to tune this particle size during the crystallization process. This paper investigates how ultrasound can control the particle size distribution (PSD) of acetaminophen crystals by continuous seed generation in a tubular crystallizer followed by batch growth. It is demonstrated that the supersaturation ratio at which ultrasound starts seed generation has a substantial effect on the final PSD while the applied power is insignificant in the studied conditions. The higher the supersaturation ratio, the smaller the final crystals become up to a supersaturation ratio of 1.56. Furthermore, it was shown that ultrasound can also impact the final PSD when applied during the growth phase. Frequencies of 850 kHz or below reduce the final particle size; the lower the applied frequency, the smaller the crystals become. In conclusion, one could state that ultrasound is able to control the particle size during seed generation and subsequent growth until the final particle size.

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Section: Nucleation In Batch Versus Flowmentioning

confidence: 99%

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

et al. 2017

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“…Ultrasound has been widely reported to influence the primary nucleation process accelerating nucleation kinetics, this is typically expressed in terms of reducing the induction time and MSZW [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Ultrasound can also increase the rate of secondary nucleation, this is manifested as a reduction on the product crystal size distribution [20,22,24,31,32,[34][35][36][37][38][39][40][41][42][43]. Ultrasound can also influence crystal growth [20,25,26,36,40,[44][45][46] although the effect on crystal growth is not as dramatic as on nucleation and arises largely from enhanced mass transfer [46] and can influence crystal morphology.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

et al. 2017

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Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol% solution of the selected impurity from 0.85 mol% to 0.35 mol% and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol% to 1.52 mol%.

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“…On the one hand, individual crystals arise due to fragmentation and disaggregation of larger crystals or aggregates [57][58][59]. On the other hand, cavitation bubbles can also act as direct nucleation sites to enhance the nuclei number [30,60]. Although this will result in smaller particles that are more prone to aggregation, the high particle loading will also effectively disrupt aggregates due to the increased number of collisions.…”

Section: Targeted Ultrasonic Treatment At Seeding Temperaturementioning

confidence: 99%

“…The benefits of this technology for crystallization were demonstrated before and include reduced metastable zone width, narrow particle size distribution and homogeneous crystal morphology [5,[26][27][28]. Although the exact mechanism of these phenomena is not yet understood, the proposed hypotheses attribute this to acoustic cavitation, involving the formation and implosion of micron-sized bubbles, and its accompanying mechanical effects [29,30]. Additional work on the effect of ultrasound during crystallization indicated that agglomeration can be suppressed, yielding individual crystals with a smooth surface [31].…”

Section: Introductionmentioning

confidence: 99%

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

et al. 2017

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Application of ultrasound during crystallization can efficiently inhibit agglomeration. However, the mechanism is unclear and sonication is usually enabled throughout the entire process, which increases the energy demand. Additionally, improper operation results in significant crystal damage. Therefore, the present work addresses these issues by identifying the stage in which sonication impacts agglomeration without eroding the crystals. This study was performed using a commercially available API that showed a high tendency to agglomerate during seeded crystallization. The crystallization progress was monitored using process analytical tools (PAT), including focus beam reflectance measurements (FBRM) to track to crystal size and number and Fourier transform infrared spectroscopy (FTIR) to quantify the supersaturation level. These tools provided insight in the mechanism by which ultrasound inhibits agglomeration. A combination of improved micromixing, fast crystal formation which accelerates depletion of the supersaturation and a higher collision frequency prevent crystal cementation to occur. The use of ultrasound as a post-treatment can break some of the agglomerates, but resulted in fractured crystals. Alternatively, sonication during the initial seeding stage could assist in generating nuclei and prevent agglomeration, provided that ultrasound was enabled until complete desupersaturation at the seeding temperature. FTIR and FBRM can be used to determine this end point.

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Experimental study of the effect of bubbles on nucleation during batch cooling crystallization

Cited by 100 publications

References 15 publications

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

Agglomeration Control during Ultrasonic Crystallization of an Active Pharmaceutical Ingredient

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